The Use of Methods of Computer-Aided Drug Discovery in the Development of Topoisomerase II Inhibitors: Applications and Future Directions.

Journal of Chemical Information and Modeling
Mariia RadaevaArtem Cherkasov

Abstract

Topoisomerase II (TopoII) is an enzyme essential for cellular metabolism and replication as it regulates DNA topology. Since inhibition of TopoII induces cell death, it is a well-established drug target in cancer therapy; several broadly used anticancer drugs including etoposide and doxorubicin are TopoII inhibitors. However, these therapeutics tend to cause severe side effects and suffer from relatively low ligand affinity, leaving TopoII targeting with small molecules an active area of research. In recent years computer-aided drug discovery (CADD) approaches have been actively used to expand knowledge on the role of TopoII in cancer and to develop novel strategies for its inhibition. Herein, we overview studies that employed structure-based approaches such as docking and molecular dynamic simulations, as well as ligand-based approaches, such as QSAR (quantitative structure-activity relationship) modeling among others, to gain understanding in TopoII targeting with existing drugs and to search for novel drug candidates.

References

Jan 1, 1983·CRC Critical Reviews in Biochemistry·L F Liu
Sep 15, 1995·The Journal of Biological Chemistry·S J Froelich-Ammon, N Osheroff
Jan 1, 1995·Cancer Chemotherapy and Pharmacology·B C BaguleyE Marshall
Mar 1, 1994·Proceedings of the National Academy of Sciences of the United States of America·J RocaJ C Wang
Jan 18, 1996·Nature·J M BergerJ C Wang
Oct 18, 1996·The Journal of Biological Chemistry·P LassotaR Kramer
Apr 4, 1997·Journal of Molecular Biology·G JonesR Taylor
Jul 4, 1998·The Journal of Biological Chemistry·J M Fortune, N Osheroff
Sep 28, 1998·Biochimica Et Biophysica Acta·J L Nitiss
Sep 28, 1998·Biochimica Et Biophysica Acta·Y PommierD Strumberg
Sep 28, 1998·Biochimica Et Biophysica Acta·T Andoh, R Ishida
Sep 28, 1998·Biochimica Et Biophysica Acta·S H Kaufmann
Dec 29, 1998·Biochimica Et Biophysica Acta·N Osheroff
Jan 20, 1999·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·K R Hande
Oct 6, 1999·Bioorganic & Medicinal Chemistry Letters·J S ZhangS T Yuan
Nov 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·C L BairdJ E Lindsley
Jan 19, 2000·Trends in Biochemical Sciences·R Dutta, M Inouye
Mar 4, 2000·Progress in Nucleic Acid Research and Molecular Biology·J M Fortune, N Osheroff
Apr 3, 2001·The Journal of Biological Chemistry·M LisbyB R Knudsen
Jun 8, 2001·Annual Review of Biochemistry·J J Champoux
Nov 28, 2001·Journal of Clinical Pharmacy and Therapeutics·Z Topcu
Apr 2, 2002·Journal of Computational Chemistry·Olgun GuvenchW Clark Still
Jun 4, 2002·Nature Reviews. Molecular Cell Biology·James C Wang
Aug 29, 2002·Nature Structural Biology·Martin Karplus, J Andrew McCammon
Jan 3, 2003·Mutation Research·Felipe CortésInmaculada Domínguez
Feb 7, 2003·Current Topics in Medicinal Chemistry·Anthony Maxwell, David M Lawson
Feb 7, 2003·Current Topics in Medicinal Chemistry·Amy M Wilstermann, Neil Osheroff
Feb 7, 2003·Current Topics in Medicinal Chemistry·William A Denny, Bruce C Baguley

❮ Previous
Next ❯

Citations

May 31, 2021·European Journal of Medicinal Chemistry·Michela PuxedduGiuseppe La Regina

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.

Cancer Metabolism: Therapeutic Targets

Targeting the mechanisms by which cancer cells acquire energy for metabolic needs is a therapeutic target. Discover the latest research on cancer metabolism and therapeutic targets.